Objective To determine the role of miR-139 in the development of hepatocellular carcinoma (HCC) and to preliminarily clarify the underlying mechanism. Methods CCK-8 assay was performed to investigate the effect of miR-139 on HCC cell proliferation. Four databases, TargetScan, MiRanda, Clip-seq and miRDB, in combination with literature review, were used to predict the downstream pathways and specifically the potential targets of miR-139. The predicted targets were then verified by Western blot analysis and luciferase reporter assay. Results CCK-8 assay confirmed that miR-139 suppressed the proliferation of HCC cells. By the comparisons between the four databases and the review of literatures, a total of five genes (ICK, BTG3, DCBLD2, EIF4G2 and HNRNPF) were predicted as potential targets of miR-139. Western blot and luciferase reporter assay validated that miR-139 could directly inhibit the expression of BTG3 in HCC cells. Conclusion miR-139 can repress the proliferation of HCC cells via directly inhibiting the expression of BTG3.